Anakinra and Intravenous IgG versus Tocilizumab in the Treatment of COVID-19 Pneumonia

  1. Massa Zantah
  2. Eduardo Dominguez Castillo
  3. Andrew J. Gangemi
  4. Maulin Patel
  5. Junad Chowdhury
  6. Steven Verga
  7. Osheen Abramian
  8. Matthew Zheng
  9. Kevin Lu
  10. Arthur Lau
  11. Justin Levinson
  12. Hauquing Zhao
  13. Gerard J. Criner
  14. Roberto Caricchio
  15. for the Temple University COVID-19 Research Group

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Abstract

Background

COVID-19 can lead to acute respiratory failure and an exaggerated inflammatory response. Studies have suggested promising outcomes using monoclonal antibodies targeting IL-1β (Anakinra) or IL6 (Tocilizumab), however no head to head comparison was done between the two treatments. Herein, we report our experience in treating COVID-19 pneumonia associated with cytokine storm with either subcutaneous Anakinra given concomitantly with intravenous immunoglobulin (IVIG), or intravenous Tocilizumab.

Methods

Comprehensive clinical and laboratory data from patients with COVID-19 pneumonia admitted at our hospital between March and May 2020 were collected. Patients who received either Anakinra/ IVIG or Tocilizumab were selected. Baseline characteristics including oxygen therapy, respiratory status evaluation using ROX index, clinical assessment using NEWS score and laboratory data were collected. Outcomes included mortality, intubation, ICU admission and length of stay. In addition, we compared the change in ROX index, NEWS score and inflammatory markers at days 7 and 14 post initiation of therapy.

Results

84 consecutive patients who received either treatment (51 in the Anakinra/ IVIG group and 33 in the Tocilizumab group) were retrospectively studied. Baseline inflammatory markers were similar in both groups. There was no significant difference regarding to death (21.6% vs 15.2%, p 0.464), intubation (15.7% vs 24.2%, p 0.329), ICU need (57.1% vs 48.5%, p 0.475) or length of stay (13+9.6 vs 14.9+11.6, p 0.512) in the Anakinra/IVIG and Tocilizumab, respectively. Additionally, the rate of improvement in ROX index, NEWS score and inflammatory markers was similar in both groups at days 7 and 14. Furthermore, there was no difference in the incidence of superinfection in both groups.

Conclusion

Treating COVID-19 pneumonia associated with cytokine storm features with either subcutaneous Anakinra/IVIG or intravenous Tocilizumab is associated with improved clinical outcomes in most subjects. The choice of treatment does not appear to affect morbidity or mortality. Randomized controlled trials are needed to confirm our study findings.

Funding

None.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.11.20192401: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The main limitation of our study is due to its retrospective, single center observational design. This design may put our study at risk for possible selection bias given no randomization to treatment or standard of care arm. Furthermore, patients were selected for each therapy depending on drug availability in our institution. The fact that we found equivalent outcomes between the two groups does provide encouragement in this regard, as real-world situations may limit the choice of drug availability at different institutions. The ubiquitous use of steroids at our institution might present a confounding factor, however anti-interleukin therapy was often added after failure of corticosteroid treatment.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04322773TerminatedAnti-il6 Treatment of Serious COVID-19 Disease With Threaten…
    NCT04315298CompletedEvaluation of the Efficacy and Safety of Sarilumab in Hospit…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.09.11.20192401v1 on medRxiv